Systematic analysis of metastatic cancer: Central mouse and in vitro projects

为了更好地了解转移，系统的分析是必不可少的。我们的目标是通过中心小鼠模型和新颖的共享技术平台紧密连接各个子项目来实现这一目标。我们将在第二个资助期使用BalbNeuT模型，包括对其进行基因修改。通过这些模型，我们努力确定转移靶器官的影响以及系统作用（免疫）机制对转移结果的影响。FOR 2127的中心目标——从动物模型到人类癌症的机制分析——将通过新技术的实施来解决。我们的目标是研究集落形成癌细胞与靶器官之间的相互作用，最初在小鼠组织培养中，随后在人体组织中。为此，我们将在C1中建立精密切割组织切片（PCTS）培养，并提供给子项目。该技术在汉诺威的弗劳恩霍夫研究所ITEM牢固地建立起来，并不断改进，将转移到雷根斯堡。通过PCTS技术，可以培养约300µm的组织切片，并暴露于各种条件下。通过与C2的合作，C1将通过添加空间转录组分析作为下游应用来扩展PCTS的功能，从而将组织切片的形态、功能和转录组信息联系起来。结合这些技术并将其应用于子项目的各种问题，我们的目标是解决早期转移形成的重要问题，以一种迄今为止不可能在人体组织中实现的方式。

For a better understanding of metastasis, systematic analyses are essential. We aim to achieve this by closely linking the various subprojects via central mouse models and novel, shared technology platforms. We will use the BalbNeuT model, including genetic modifications of it, also in the second funding period. With these models we strive to identify the impact of metastatic target organs as well as systemically acting (immune-) mechanisms on the outgrowth of metastasis. The central goal of FOR 2127 - to proceed from animal models towards a mechanistic analysis of human cancer - will be addressed by the implementation of novel technologies. We aim to investigate interactions between colony-forming cancer cells and target organs initially in murine tissue cultures and subsequently in human tissues. For this we will establish the precision cut tissue slice (PCTS) culture in C1 and provide it for the subprojects. The technology is firmly established at the Fraunhofer institute ITEM in Hannover, has been improved continously and will be transferred to Regensburg. By PCTS technology tissue sections of about 300 µm can be cultured and exposed to various conditions. In collaboration with C2, C1 will extend the power of PCTS by adding spatial transcriptomic analysis as downstream application, which allows to link morphological, functional and transcriptomic information of the tissue slices. Combining these technologies and applying it to various questions of the subprojects we aim to address important questions of early metastasis formation in a way that has not been possible with human tissues so far.